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Antibiotic-resistant bacteria are on the rise. At the same time, antibiotic drug development has slowed to a crawl. We’re definitely in trouble and must preserve our last antibiotics.

Little did I know when I set out to report this story last February for the Canadian Journal of Medical Laboratory Science that within days, the World Health Organization would publish a list of a dozen antibiotic-resistant superbugs that pose the greatest threat to human health. The WHO warned drug manufacturers and frontline infection-control healthcare workers to focus on the most dangerous superbugs first.

Then my story sources told me about a patient who was infected with a superbug listed near the top of the critical list. The story arc for the article fell neatly into place.

Antibiotic-resistant bacteria have several nasty tricks up their sleeves to evade destruction. They can develop cellular pumps that push infiltrating antibiotics back out. Some produce a slimy coating to avoid detection. Others even swap plasmids, small rings of DNA, with other bugs to pass on antibiotic-resistance superpowers.

What does good antibiotic stewardship involve? A team approach coordinated between infectious disease doctors, nurses and medical laboratory technologists can help identify the pathogen quickly, establish susceptibility and ensure treating patients with the right drug for the right length of time.

The next time you feel like pressing your doctor for an antibiotic prescription for the flu or the common cold, think again. Antibiotics are not necessarily required in surgeries either: my surgeon did not prescribe any before or after my foot surgery for cartiva implants in both feet nine months ago.

Click on the story below to read how the healthcare team helped this patient who was out of all other options.

You have probably heard about the Ebola epidemic that began in West Africa in early 2014 and continues today. But I bet you have never heard about an Ebola scare in Saskatoon that happened only a few days after the outbreak began in March 2014.

For this story for The Canadian Journal of Medical Laboratory Science, I spoke to Dr. Joseph Blondeau, Acting Department Head for Pathology and Laboratory Medicine with Saskatoon Health Region and Mary-Louise Graham, Director for the Office of Biosafety and Biocontainment Operations, Centre for Biosecurity at the Public Health Agency of Canada.

It was an extremely tense 48 hours. ~Dr. Joseph Blondeau

A patient with an unknown viral hemorrhagic fever arrived at a Saskatoon hospital, late one Sunday night. The patient’s condition was deteriorating rapidly — he had a diffuse rash, fever and was bleeding from the eyes. His medical history was difficult to obtain, but one thing stood out — he had recently returned from Liberia, the Ebola hot zone, within the 2-21 day incubation period for the disease.

To further complicate things, this was happening in Saskatoon, Saskatchewan, where there was no authorized courier that could transport blood specimens to the only Containment Level 4 lab in Canada, located in Winnipeg, Manitoba, a 10-hour drive away.

As of July 15, 2015, there have been 27,688 reported cases and more than 11,279 deaths, according to the CDC.

Click on the image below to read the whole story and find out what happened.

My son emailed me this week to ask if he had been immunized for measles when he was little. He’s working for a Silicon Valley tech company for a co-op work term. His employer had issued a notice that an employee in another building has contracted measles, so he wondered if he is at risk.

Digging out his immunization record, I could see that he’d had the first MMR (measles mumps rubella) vaccine shortly after his first birthday and a second shot when he was 6 years old.

This wasn’t the first time I needed to look back at a paper health record for my kids, though.

My daughter had a similar question years earlier. She had applied for a volunteer position at a hospital in her university town and needed a signed letter from our family doctor to verify that her immunizations were up to date. But he was unable to find her records in the clinic’s mess of paper files and said he would provide a letter if she could come back with records from MY files.

I still have both kids’ little yellow leaflets. Our first family doctor had filled out the information in the early days, but later doctors just told me to enter the information myself and not lose them.

Our family doctor belongs to a clinic where the owners of the practice are dragging their heels to convert to electronic health records. According to eHealth Ontario’s Progress Report, 2 out of 3 Ontarians are covered by electronic medical record (EMR) software and 7 out of 10 physicians use EMR software in their practice. Just not our family doctor yet.

I agree with taking responsibility for personal health, but I’m surprised to learn that vaccines and ultimately herd immunity against infectious diseases depend on the honour system. I never would, but in theory, I could have falsified my daughter’s information with no checks in the system to verify. Patients at that hospital might have been at risk if she was not really up to date. Given our experience with immunization records, any prediction of vaccination rates in specific geographic areas is a guess.

In Canada, we have no national vaccine registry. A large project called Panorama, envisaged more than five years ago to track things like immunization coverage, disease outbreaks and vaccine supplies, has been stalled by setbacks and adopted on a piecemeal basis—some provinces are adopting parts and others have declined participating altogether.

I hope that someday, immunizations will be part of our digital health records for two reasons—easier access and accuracy. In the meantime, I’m glad my family is up to date.

The number of newly approved antibiotics has declined significantly since the 1980s as large pharmaceutical companies have mostly withdrawn from research and development in this critical market segment. Fortunately, the biotech industry is now stepping up to the plate to develop much-needed antibiotics to fight a rising number of drug-resistant superbugs, such as Clostridium difficile (or C. difficile).

Optimer Pharmaceuticals, Inc. of San Diego, CA recently received FDA approval for Dificid (fidaxomicin), a narrow spectrum antibiotic tablet to treat C. difficile-associated diarrhea. In clinical studies reported in the New England Journal of Medicine, patients treated with Dificid had a high cure rate of 90%, similar to standard vancomycin treatment, but with a significantly lower rate of recurrence: 13.3% versus the vancomycin group who showed a recurrence rate of 24.0%.

Dificid is the first in a new class of antibiotics called macrocycles, engineered to target C. difficile specifically. Sherwood Gorbach, MD, Chief Medical Officer for Optimer and co-author of the studies says, “because fidaxomicin is a narrow spectrum antibiotic, there is less likelihood to produce resistance, a problem we see with vancomycin.” Optimer holds patents for developing the unique fidaxomicin compound from a fungus found in soil.

The elderly and people in hospitals who have been treated with antibiotics are most at risk because C. difficile gets a chance to flourish and produce toxins in the gut after antibiotics have wiped out normal gastrointestinal flora. At any given time, about half of the patients in a hospital are receiving antibiotics.

The spread of infection can be difficult to contain as the spores can live outside the human body for a long time and may be found on hard surfaces such as bed linen or medical equipment. While C. difficile is mainly a hospital-acquired infection, about one-third of cases are found in long-term care facilities such as rehabilitation centers and nursing homes.

Recurrence is a significant problem as the symptoms are often worse than the original bout of infection. Gorbach emphasizes, “the reduction in the rate of recurrence is a significant advancement for patients with CDI. Fidaxomicin showed a sustained clinical response for 25 days, the period following treatment when most recurrences happen, in a greater number of cases vs. vancomycin.”

Another current therapeutic option for treating CDI is the off-label use of metronidazole, recommended by the CDC as an alternative to vancomycin. It has been around since the 1950s and has never been submitted to the FDA for approval for C. difficile treatment. Although not tested in clinical studies, according to Gorbach, Dificid offers a more promising treatment option, “Metronidazole is well absorbed, and so a lot of patients taking it experience side effects, whereas the side effects with fidaxomicin are very rare, because it is not readily absorbed.”

Recently in Canada, there have been more outbreaks of a hypervirulent C. difficile strain, variously referred to in the media as NAP1/BI/027. Over the past summer, that strain was responsible for an outbreak that led to more than 30 deaths in the Niagara, Ontario area. NAP1/BI/027 was the culprit identified between 2002-2004 in Quebec hospitals, where hundreds of patients were infected and several deaths occurred. The CDC also reported outbreaks of NAP1/BI/027 in several states in 2004.

While Dificid is not yet approved for sale in Canada, Optimer is currently in consultation with Health Canada to determine if Dificid can offer some assistance to combat NAP1/BI/027. In the clinical studies, about 35% of the patients had the NAP1/BI/027 strain of C.difficile. Analysis of the data from two of the clinical trials showed that further investigation is required: one study showed Dificid was superior to vancomycin for reducing recurrences of the hypervirulent strain, but the other study showed equal results.

Update: Dificid tablets were approved by Health Canada on July 5, 2012, the first new treatment for C. difficile infection in Canada in over 20 years. “Awareness of the burden of CDI on the Canadian health care system is high with many health care providers, patients, and caregivers impacted by this devastating infection,” said Paulash Mohsen, President and Country Manager for Optimer Canada. “This familiarity with CDI will help us as we make DIFICID available to Canadian patients in need.”

If you had latent tuberculosis—infection with TB bacteria that could flare up into active disease–which treatment therapy would you choose: a three-month therapy of 12 weekly doses or a nine-month therapy of 270 daily doses?

According to a multinational study by the Centers for Disease Control and Prevention, people with latent tuberculosis (TB) now have access to a new, faster regimen with fewer doses. Seen as one of the biggest developments in TB treatment in decades, the PREVENT TB study shows that the new regimen is as safe and effective as the longer standard therapy, and it has a significantly higher rate of completion. The research results were presented at the American Thoracic Society 2011 International Conference in Denver, Colorado.

TB is an airborne infectious disease caused by the bacterium Mycobacterium tuberculosis. The bacteria usually invade the lungs but can also attack the kidney, spine or brain. It is one of the deadliest diseases in the world — one-third of the world’s population is infected with TB and there are almost 2 million TB-related deaths on a global basis each year.

In the United States, there were 11, 181 reported cases of TB in 2010, down significantly from the 84, 304 cases reported in 1953 when the disease was first tracked by the CDC. Approximately 11 million Americans are infected with latent TB, but many are unaware as it can only be found by a positive reaction to a TB blood or skin test.

Latent TB infection occurs when a person has TB bacteria in their body but has no symptoms and cannot transmit the bacteria to others. About 10% of people who have latent TB infection will go on to develop active TB disease, which may include symptoms such as a bad cough that lasts for weeks, pain in the chest, coughing up blood or sputum, chills, fever and sweating at night.

The PREVENT TB study was one of the largest CDC-sponsored clinical trials, taking over 10 years to complete. It involved 8,053 participants from countries with low to medium incidence of TB, with the majority from the United States and Canada. Dr. Reichman points out that given how slowly TB grows and the fact that only 10% of those infected with latent TB will develop active TB, “It’s pretty ingenious that these studies were put together by the TB Trials Consortium 10-15 years ago.”

The new regimen of a once weekly, directly supervised therapy of rifapentine taken together with isoniazid for 3 months has proven to be as safe and effective as the standard therapy of daily, self-administered isoniazid alone for 9 months. Very few cases of TB developed in either the test group taking the new regimen (7) or the control group taking the standard treatment (15). Importantly, the rate of treatment completion was significantly higher at 82% for the new regimen group, compared to 69% in the standard therapy group.

Researchers note that study results only apply to countries with low to medium incidence of TB and further research is needed before the new regimen can be recommended in countries where there is a high incidence of TB. Treatment guidelines for the new regimen are expected later this year, but are anticipated to include the recommendation that the drugs be administered under direct supervision, as tested in the study group.

Dr. Reichman says, “People may think that we don’t get TB anymore, but they don’t realize, the reason why we don’t is due to new regimens like this. If we don’t continue our vigilance against TB, it’s going to come back with a vengeance.”

CONNECT THE DOTS

GE scientists in Bangalore, India, Shanghai, China, and Niskayuna, New York are investigating to see if existing technologies can be leveraged to provide a rapid point-of-care diagnostic test for TB. Read our earlier post Tuberculosis, New Weapons Against an Old Disease. Visit the CDC site for Tuberculosis or check out the WHO’s Stop TB Strategy, a global initiative to reduce the burden of TB by 2015.

This story was published on GE Healthy Outlook last spring after the FDA approved INCIVEK. I spoke with Jordan Feld, MD MPH, hepatologist at the Toronto Western Hospital Liver Clinic and clinician scientist at the McLaughlin-Rotman Centre for Global Health at the University of Toronto, to find out what this new drug could mean for patients with hepatitis C.

The FDA has approved a new drug called INCIVEK (telaprevir) for adults with difficult-to-treat genotype-1 chronic hepatitis C. Clinical trials showed a significantly better outcome for both people who had never received standard therapy before, as well as those who had previously received standard therapy but did not respond adequately. INCIVEK is a major breakthrough given that less than 50% of patients respond to the standard therapy.

Jordan Feld, MD, MPH is a hepatologist at the Toronto Western Hospital Liver Clinic and a clinician scientist at the McLaughlin-Rotman Centre for Global Health at the University of Toronto. He says, “The introduction of telaprevir as a direct acting antiviral drug is a huge advance for patients who have hepatitis C. This drug increases the rate of response and can shorten treatment for about two-thirds of patients.”

In the clinical studies, 79% of patients who had never been treated before achieved a viral cure after treatment with INCIVEK together with standard therapy, compared to 46% in the control group, who received a placebo plus standard therapy. INCIVEK is a direct-acting antiviral drug that works by inhibiting protease, an enzyme necessary for the hepatitis C virus to replicate. INCIVEK must be administered together with peginterferon and ribavirin (the current standard interferon therapy), to help prevent the virus from becoming resistant.

Hepatitis means inflammation of the liver. Hepatitis C virus is the most common blood infection in the United States: about 3.2 million people are chronically infected and infection rates are highest among those born between 1945-1965. Globally there are six different genotypes of hepatitis C virus, but genotype 1 accounts for about 70% of the cases in the United States.

The majority of infected people may not even know they are infected, but they can still transmit the disease to others and can develop chronic liver disease 20-30 years or more after infection. If symptoms occur from a newly acquired infection, they can include fever, fatigue, dark urine, abdominal pain, loss of appetite and jaundice. Chronic liver disease can lead to cirrhosis, liver cancer, the need for a liver transplant, or even death.

Hepatitis C virus is most often transmitted through exposure to infected blood, which can be contracted from contaminated needles used for tattoos, injection drugs or even vaccines for childhood infections in countries with poor medical care. Hepatitis C was commonly spread through blood transfusions and organ transplants before blood screening started in 1992.

Dr. Feld points out “while there’s no question INCIVEK is a huge advance, it is not a panacea. Those cure rates of 70% and higher are not for everybody.” Dr. Feld was not involved in the telaprevir studies, however his liver disease research focuses on trying to understand response to interferon based therapy, with or without protease inhibitors. Success rates for achieving a viral cure in the clinical studies depended on whether or not the patient had been treated before with standard therapy, how they responded, and if they had more advanced disease characterized by cirrhosis or scarring of the liver. For example, for those who did not respond at all to a previous standard therapy and had cirrhosis, only 14% achieved a viral cure.

Shorter treatment for 24 weeks, rather than the current standard of 48 weeks is a welcome relief for those patients who qualify, because the side effects of peginterferon and ribavirin are challenging because they are similar to having influenza – body ache, fever and headache. Whether a patient qualifies for the shorter treatment depends on their past history of treatment, and whether they are showing early response to the INCIVEK combination therapy as monitored in their blood work at weeks 4 and 12.

The most frequent adverse reactions in the test groups were rash and anemia. While rash developed in 56% of patients who received the INCIVEK combination treatment, only 4% reported a severe rash and only 1% discontinued treatment due to rash. Only 1% of those taking INCIVEK discontinued therapy due to anemia.

The FDA approval of INCIVEK is a significant breakthrough for curing hepatitis C infection. As a direct acting agent specifically targeted to attack the hepatitis C virus, INCIVEK offers a better chance for a viral cure and the possibility for a shorter treatment.

This is my health news story published last spring on GE Healthy Outlook about the first rapid diagnostic test for the highly resistant superbug MRSA.

New technology test helps fight infection sooner

MRSA, or methicillin-resistant Staphylococcus aureus, isa superbug bacteria that is highly resistant to antibiotics like methicillin. MRSA emerged in health care settings in the 1960s, but it is now also commonly found in skin infections in the general community. A severe MRSA infection can be life threatening, especially if it develops into a bloodstream infection or pneumonia.

The FDA recently cleared the KeyPath MRSA/MSSA Blood Culture Test, the first test that can quickly identify and distinguish MRSA from MSSA (methicillin susceptible SA). This new test, manufactured by MicroPhage, can make a determination and distinction about five hours after bacterial growth is first found in a blood sample. Current test methods depend on lengthy procedures to isolate and then identify bacteria. This new test is up to two days quicker, as the Bacteriophage Amplification Technology speeds up the process while exposing the bacteria to antibiotics to determine susceptibility.

The KeyPath MRSA/MSSA Blood Culture Test was evaluated in a clinical study of 1, 116 blood samples evaluated at four major U.S. hospital centers. Within bacteria that were identified as Staphylococcus aureus, the MRSA determination was 98.9% accurate, and the MSSA determination was 99.4% accurate.

Making a quicker determination of MRSA or MSSA is critical because the mortality rate for bloodstream infections of Staphylococcus aureus is in the range of 30-40%. Right now, up to half of all suspected cases are initially prescribed suboptimal or inappropriate antibiotics until test results are available. Edward Dominguez, MD and Medical Director for Organ Transplant Infectious Diseases at the Methodist Dallas Medical Center says, “Drugs like vancomycin that we use to fight MRSA take much longer to act, about 4-5 days, compared to penicillin-class drugs which are superior to vancomycin for clearing an MSSA infection. If this test can identify the infection as an MSSA sooner, we can switch the treatment to a more targeted antibiotic earlier, and we should be able to clear the infection in 2-3 days.”

Dr. Dominguez says that doctors are looking for ways to reduce the over-use of drugs like vancomycin, as there is evidence that vancomycin-resistant strains of Staphylococcus aureus are emerging. He also points out that in the early 1900s, before antibiotics were invented, 9 out of 10 people died from bloodstream infections. Dominguez says, “A lot of people don’t realize that the upside risk of MRSA is huge. There is a 90% mortality rate if we don’t have antibiotics that are effective – it’s a deadly disease.”

A study published in the New England Journal of Medicine in 2006 found that among those adults who visited hospital emergency departments in major U.S. cities with active skin infections, 59% of them on average were infected with MRSA, and 99% of those MRSAs were community-associated MRSA types.

A MRSA skin infection can appear as a bump or infected area on the skin and may be mistaken for a spider bite. The infection may be red, swollen, painful, warm to the touch, full of pus, or accompanied by a fever. While MRSA is more prevalent than ever before, the earlier it is caught and treated, the better the outcome. Good hygiene practices can help prevent MRSA infections. The Centers for Disease Control and Prevention provides specific recommendations to help prevent MRSA infections in a variety of community settings.

CONNECT THE DOTS

Listen to a public service radio announcement about MRSA by the Department of Health and Human Services’ Centers for Disease Control and Prevention. Visit the CDC’s website to learn more about MRSA including causes, symptoms, treatment and prevention recommendations.

Originally published on GE Healthy Outlook, June 7, 2011. Copyright Jane Langille.

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